Type 1 diabetes mellitus (T1DM) is caused primarily by autoimmune destruction of insulin-producing pancreatic beta-cells,1-3 and in some cases, also by non-immune related severe insulin deficiency.4 Although the presence of several genotypes on the human leukocyte antigen alleles indicate predisposition to T1DM,5-8 and increasing evidence points to environmental triggers such as exposure to enterovirus and the composition of early childhood diet,9-14 the etiology of T1DM remains unknown.
It has been estimated that only 20% of β cell mass remains at the time of presentation of clinical T1D symptoms,1 which is typically preceded by an asymptomatic period of highly variable duration from a few months to more than 10 years.15 The appearance of several autoantibodies to specific islet antigens is the first detectable sign of emerging beta-cell autoimmunity.9 These autoantigens include glutamic acid decarboxylase (GAD), protein tyrosine phosphatase (IA-2), insulin and most recently, the zinc transporter Slc30A8 protein.4,6,16 Multiple autoantibody positivities and their persistence are unequivocally related to the risk of progression to overt T1DM, both in family studies and also in surveys of general population cohorts.1,17,20 However, islet autoantibody assays are difficult to perform with consistent high sensitivity and specificity, and performance at different sites varies considerably despite multiple efforts to standardize these assays by the Diabetes Antibody Standardization Program (DASP) and the Type 1 Diabetes Genetics Consortium.21-23 In addition, not all islet autoantibody-positive subjects progress to T1DM.17,20,24 